|Year : 2016 | Volume
| Issue : 1 | Page : 33-38
Environmental factors other than iodine deficiency in the pathogenesis of endemic goiter in the basin of river Ganga and Bay of Bengal, India
Amar K Chandra1, Arijit Debnath1, Smritiratan Tripathy1, Haimanti Goswami1, Chiranjit Mondal1, Arijit Chakraborty1, Elizabeth N Pearce2
1 Department of Physiology, Endocrinology and Reproductive Physiology Laboratory, University of Calcutta, Kolkata, West Bengal, India
2 Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, Massachusetts, USA
|Date of Submission||15-Apr-2016|
|Date of Acceptance||10-May-2016|
|Date of Web Publication||2-Jun-2016|
Amar K Chandra
Department of Physiology, Endocrinology and Reproductive Physiology Laboratory, University of Calcutta, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
Background: In iodine-replete basin of the river Ganga and the Bay of Bengal, we studied iodine nutritional status of school children by goiter prevalence and their urinary iodine (UI), iodine content in edible salt, and the bioavailability of iodine through water and its contribution to iodine nutrition. We also studied consumption pattern of common goitrogenic plants by measuring urinary thiocyanate (USCN), hardness of water (calcium and magnesium salt content) and assessed the effect of concomitant exposure of those environmental factors in goitrogenesis.
Methods: 4603 children aged 6-12 years were examined for goiter by palpation, 520 urine samples were analyzed for UI and USCN; iodine content was estimated in 455 household salt and 130 water samples tested both for iodine and hardness.
Results: The total goiter rate was 35.9%, median UI was 231 ΅g/l, mean USCN was 0.857 ± 0.48 mg/dl, iodine content in water was 44.7 ± 4.1 ΅g/l, 66.4% of salt samples contained iodine (15 ppm), and water was found to be hard. UI was correlated with both the drinking water iodine content and USCN and the degree of hardness in drinking water was associated with goiter prevalence.
Conclusions: The studied population has endemic goitre despite iodine sufficiency. The concomitant exposure of a number of environmental factors, i.e., thiocyanate of cyanogenic plant food, hardness of drinking water, and excess iodine from environmental sources other than iodide salt are likely responsible for the causation and persistence of endemic goiter in the region.
Keywords: Basin of Ganga, endemic goiter, environmental goitrogens, excess iodine, thiocyanate, water hardness
|How to cite this article:|
Chandra AK, Debnath A, Tripathy S, Goswami H, Mondal C, Chakraborty A, Pearce EN. Environmental factors other than iodine deficiency in the pathogenesis of endemic goiter in the basin of river Ganga and Bay of Bengal, India. BLDE Univ J Health Sci 2016;1:33-8
|How to cite this URL:|
Chandra AK, Debnath A, Tripathy S, Goswami H, Mondal C, Chakraborty A, Pearce EN. Environmental factors other than iodine deficiency in the pathogenesis of endemic goiter in the basin of river Ganga and Bay of Bengal, India. BLDE Univ J Health Sci [serial online] 2016 [cited 2020 Sep 30];1:33-8. Available from: http://www.bldeujournalhs.in/text.asp?2016/1/1/33/183283
Implementation of the universal salt iodization program in a region without the proper knowledge to its environmental iodine status is a major concern since excess iodine ingestion in several regions during post salt iodization phase is associated with chronic autoimmune thyroiditis, hypothyroidism, and other thyroid disorders. , A retrospective study in school children from the Sundarban delta in West Bengal reported a high prevalence of goiter (38.2% and 33.1%, respectively, in South 24 and North 24 Parganas Districts of Sunderban delta) though they had no nutritional iodine deficiency as evidenced by their urinary iodine (UI) excretion. , Based on our preliminary survey of iodine deficiency disorders (IDDs) in the basin of the river Ganga and the Bay of Bengal, 13 Community Development (CD) blocks were selected on opposite sides of the Sundarban delta. Besides examining iodine nutritional status by goiter prevalence and UI excretion pattern, distribution of iodine through household salt, consumption of common goitrogenic plant foods (thiocyanate precursors), and hardness of drinking water (presence of total calcium and magnesium salts in water), since it has been hypothesized that all these may interfere iodine metabolism. Further, the correlation between drinking water iodine content and UI content to understand the contribution of environmental iodine in iodine nutrition, association between urinary thiocyanate and UI levels to understand the impact of thiocyanate in iodine excretion, and to study the relationship between hardness of drinking water and total goiter rate to understand the involvement of water hardness in goitrogenesis. Finally to examine the combined effects of those pro-goitrogenic agents found in food and water of the region on thyroid disruption.
| Materials and Methods|| |
Selection of study areas
Thirteen CD blocks located in the basin of the river Ganga and the Bay of Bengal in the Howrah and Purba Midnapore districts of West Bengal on the opposite sides of the Sunderban delta were selected. The total population of this region is 31, 50, 357 (2001 census). Most of the population is engaged in agricultural activities, fisheries, and to a certain extent, working in factories such as the Haldia oil refinery. Local diets are mainly nonvegetarian and consist primarily of cereals (rice), pulses, fish, and vegetables of the Brassica family. The study was conducted between November 2010 and August 2013.
Selection of population
To obtain proper representation, one locality was randomly selected from each of thirteen CD blocks.  In each locality, one primary school and the nearest adjoining secondary school were selected at random  so that students aged 6-12 years of both sexes would be available as recommended by the WHO/UNICEF/ICCIDD.  Ethical clearance for the study was obtained from the Institutional Ethical Committee.
Clinical goiter survey
A total of 4603 students were examined for goiter by palpation. The clinical examination for goiter was conducted by two trained research staffs experienced in IDD survey methodology. Goiter grading was done according to the criteria recommended by WHO/UNICEF/ICCIDD  (Grade 0: No goiter; Grade 1: Thyroid palpable but not visible; and Grade 2: Thyroid visible with the neck in normal position). The age of the students was recorded from the school register and was rounded to the nearest whole number.
Iodine and thiocyanate in urine
Five hundred and twenty spot casual urine samples were collected from the examined children (40 from each locality), maintaining proportionate representation from the entire population of the studied school(s).  A drop of toluene was added to each urine sample to inhibit bacterial growth and to minimize odor. Iodine concentrations in urine were determined by the arsenite method following dry ashing in the presence of potassium carbonate.  Thiocyanate content in the urine was measured from the same urine samples analysis by the method of Aldridge  as modified by Michajlovskij and Langer. 
Iodine in salt and water
Local sources of dietary iodine are water, food, and iodized salt. To monitor the iodine content of salt available in the area, 35 marked air tight plastic containers were distributed at random to students of the studied schools in each locality, and they were asked to bring edible salt samples from their households the next day. The salt samples were kept at room temperature in the laboratory and iodine content was measured within a week following the iodometric titration method.  One hundred and thirty drinking water samples were collected at random (10 samples from each area)  and kept at 4°C until iodine concentrations were measured using the method of Karmarkar et al. 
Hardness of drinking water
Hardness of drinking water (total calcium and magnesium salt content) was measured from the 130 drinking water samples. On the day of analysis, all the collected ten samples in an area were mixed properly and then hardness was measured following the EDTA titration method. 
Descriptive data include means, standard deviations, medians, and ranges, as appropriate. Pearson correlations were used to examine univariate associations.
| Results|| |
A total of 4603 children were examined in the age group 6-12 years. Out of 4603 school children (50.9% were boys and 49.03% were girls), goiter was detected in 1656 (35.9%) of them. Grade1 goiter was present 31.5% and Grade 2 was present in 4.4% of the children [Table 1]. The studied population of all the 13 localities in coastal districts was homogenous with respect to geographical characteristics, economic status, and dietary practices.
|Table 1: Goitre prevalence of different study localities in the basin of river Ganga and Bay of Bengal, India|
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Urinary iodine and thiocyanate
Median UI concentrations of the studied localities ranged from 132.5 to 350 μg/L in 520 urine samples, indicating that the population had no nutritional iodine deficiency as median UI levels were above 100 μg/L in all study localities. The mean urinary thiocyanate levels ranged from 0.656 ± 0.359 to 1.130 ± 0.620 mg/dl in the studied urine samples. The median and mean iodine and thiocyanate level of the overall studied population were 231.3 μg/l and 0.857 ± 0.486 mg/dl, respectively [Table 2].
|Table 2: Urinary iodine and thiocyanate excretion of studied population, iodine content in salt, iodine content and total hardness in drinking water of different study localities in the Basin of river Ganga and Bay of Bengal, India|
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Iodine content in edible salt and water
The proportion of salt samples containing ≥15 ppm iodine ranged from 40 to 94.5%; overall, 66.4% households were consuming salt with adequate iodine. In other words, in most of the study localities iodine supplementation through household salt was not satisfactory [Table 2]. However, no salt sample was found without iodine.
A total of 130 drinking water samples were collected from 13 study localities taking 10 samples from each locality and were analyzed for iodine content which were in the range of 6.9±1.6 - 92.5±5.1 ΅g/l with a mean iodine level of 44.7 ± 4.1 μg/l [Table 2].
Hardness of water
The hardness of drinking water samples (total calcium and magnesium salts present) collected from the different study localities ranged from 210 ± 15.6 ppm to 618 ± 23.3 ppm [Table 2].
Correlation between iodine content in drinking water and UI content of the population, between urinary thiocyanate excretion levels and UI level, and between the hardness of drinking water and the total goiter rate of the population are shown in [Figure 1],[Figure 2] and [Figure 3], respectively. A positive correlation (r = 0.472; P < 0.05) was found between drinking water iodine content and UI concentrations of the population [Figure 1]. Further, a significant positive correlation (r = 0.158; P < 0.001) was found between urine thiocyanate and iodine concentrations [Figure 2]. Finally, a highly significant positive correlation (r = 0.544; P < 0.001) was found between the total hardness of drinking water and goiter prevalence [Figure 3].
|Figure 1: Relationship between drinking water iodine content and urinary iodine concentrations of the population in the basin of the river Ganga and Bay of Bengal|
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|Figure 2: Relationship between urinary thiocyanate excretion and urinary iodine levels of the population in the basin of the river Ganga and Bay of Bengal|
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|Figure 3: Relationship between drinking water hardness and total goiter rate of the population in the basin of the river Ganga and Bay of Bengal|
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| Discussion|| |
The purpose of this study is to explore the combined effects of a number of environmental goitrogenic agents found in food and water on thyroid disruption developing goiter in the population of the basin of the river Ganga and Bay of Bengal in the coastal region of West Bengal.
In general, the size of the thyroid gland is inversely associated with iodine intake, with a lag interval that varies from a few months to several years, depending on many factors. These include the severity and duration of iodine deficiency, the type and effectiveness of iodine supplementation, and possible additional goitrogenic factors (WHO/UNICEF/ICCIDD).  The overall total goiter rate of 35.9% among school-children in our study indicated that endemic goiter/IDD is severe and a major public health problem in the basin of river Ganga and Bay of Bengal. In 11 out of 13 studied localities, the prevalence of goiter (>30%) indicated that IDD was severe and other two localities it was moderate, as goiter prevalence was >20%.
About 90% of ingested iodine eventually appears in urine and thus UI excretion is a good marker of very recent dietary iodine intake. In individuals, UI excretion typically varies from day to day and even within a given day.  In general, 30 urine iodine concentrations, from a defined sampling group are sufficient to understand the status of iodine nutrition (WHO/UNICEF/ICCIDD).  The RDA for iodine is 150 mcg in adults.  In school-aged children, median urinary concentrations between 100 and 199 μg/l define a population having adequate iodine nutrition but concentrations in between 200 and 299 μg/l are consistent with more than adequate, and median UI concentrations ≥300 μg/l are considered to be excessive and are associated with risk for adverse health consequences (iodine-induced hyperthyroidism, autoimmune thyroid diseases, etc.).  Of the 13 studied localities, 3 localities had adequate iodine nutrition, six had more than adequate iodine nutrition, and in the remaining four localities iodine nutrition was excessive. The excessive environmental iodine present in the water of this coastal region contributes iodine more than adequate level and thus responsible for thyroid enlargement [Figure 1]. Excess iodine may exist naturally such as that reported in costal Hokkaido in Japan where goiter was found to be endemic among the children.  Further, an association between excess iodine intake, increased serum thyroid stimulating hormone (TSH) and thyroid volume was detected in China where drinking water is rich in iodine.  Excess iodine consumption can also result from additional supplies of iodine for intake in the different form of fortified food.  Distribution of iodized salt poorly monitored for the iodine concentration resulted in excess iodine intake in Iceland. 
It has been recommended that at least 90% of the households should have access to iodized salt at the recommended level of 15 ppm.  This study showed that in overall only 66% of total households were consuming salt with adequate iodine [Table 2]. Therefore, the supply of dietary iodine through salt was not satisfactory; however, the iodine nutritional status of most of the studied population in the study localities was above requirement and even excessive, indicating that the population must have other significant sources for iodine intake. The people of this coastal area are mainly rural, and they consume foods that are largely cultivated locally. Iodine content in the agricultural products of a region is known to be dependent on iodine content in the soil. Iodine content in the drinking water indicates that this coastal region is environmentally iodine sufficient or the soil rich in iodine.  Drinking water iodine content of the study localities found positively correlated with UI concentrations of the population. Therefore, iodine present in drinking water not only compensates the inadequacy of iodine in locally-available iodized salt but also supplies more than adequate iodine to the population.
The prevalence of goiter among the studied population was high despite the supplies of adequate dietary iodine, suggesting the presence of dietary goitrogens and/or naturally occurring antithyroidal/goitrogenic agents in food and drinking water. To look into this aspect, we measured the thiocyanate excretion pattern of the population and hardness of drinking water.
Thiocyanate, one of the best known and widely studied goitrogen responsible for causation or aggravation of endemic goiter especially in a relatively or severely iodine-deficient region.  However, a successful salt iodine fortification program failed to prevent goiter development in school children from Manipur in Northeast India due to the high level of consumption of bamboo-shoots, food containing thiocyanate and thiocyanate like compounds.  Thiocyanate has also been implicated as goitrogenic factor in Tripura,  another northeastern state of India, sub-Himalayan tarai region in Uttar Pradesh  and even in the iodine replete Sundarban delta of Gangetic West Bengal , just on the opposite side of the study area. The foods contributing thiocyanate were cabbage, cauliflower, radish, mustard seeds and leaves, sweet potatoes, turnip, etc., Thiocyanate (SCN) competitively inhibits the iodine-concentrating mechanism of the thyroid. SCN has also been reported to increase iodine efflux,  and to interfere with the activity of thyroid peroxidase (TPO)  and the incorporation of iodine into thyroglobulin by competing with iodide.  It also causes the formation of insoluble iodinated thyroglobulin in thyroid.  The present investigation revealed that the mean urinary thiocyanate of the children was 0.857 ± 0.486 mg/dl, which is much higher than the thiocyanate concentration in urine of populations in India without endemic goiter (0.504 ± 0.197 mg/dl). 
Thiocyanate not only interferes with iodine utilization in the thyroid gland, but also facilitates the removal/excretion of iodine from the body by inhibiting the iodine uptake into the thyroid.  In this study, a significant positive correlation was found between urinary excretion of thiocyanate and iodine [Figure 2]. Thus, SCN present in plant foods consumed by the people of the region may be one of the factors in the pathogenesis of goiter.
In the studied areas, the water used for drinking/cooking was found to be hard, with the local ranges of 210-618 ppm in excess of the threshold value of 200 ppm as defined by Indian drinking water specifications.  High mineral content, particularly of magnesium and calcium salts, has been implicated as a goitrogenic factor in several endemic goiter areas. , Murray et al.  concluded on the basis of their studies that even where the iodine intakes were similar, there was a greater prevalence of visible thyroid glands in people in areas with hard water such as England, than in areas with soft water, such as Scotland. The presence of excess calcium in the colloid of the thyroid follicle causes compactness of thyroglobulin molecules (containing T3 and T4) in follicular cells and their subsequent release in circulation.  In a recent study conducted in our laboratory, we found that excess calcium causes enlargement of the thyroid with hypertrophic and hyperplastic changes, retarded TPO and 5'-deiodinase, but enhanced Na-K-ATPase activities, augmented serum total and free T4 and TSH but decreased total and free T3 levels, and a low T3:T4 ratio, resulting in goitrogenesis.  A highly significant positive correlation was found between the total hardness of drinking water and goiter prevalence [Figure 3] indicating that hardness of drinking water may have a direct role in the pathogenesis of goiter in the studied region. Thus, in addition to excess iodine and thiocyanate in food, drinking water hardness may have the important role in the pathogenesis of endemic goiter.
Available literature shows that thiocyanate of food or hardness of drinking water or relatively excess iodine intake may decrease thyroid hormone levels, and has less impact on thyroid gland functions; however, the concomitant exposure of those multiple environmental agents may aggravate thyroid disruption as found in the present investigation.
Our results demonstrated that the population of the studied region has a high level of endemic goiter despite the absence of iodine deficiency for the concomitant exposure of at least three progoitrogenic factors viz. thiocyanate, water hardness, and iodine excess. All these act at the different levels of thyroid hormone synthesis causing an interruption in the production of a hormone that in the long run leads to enlargement of the gland by compensatory mechanism developing a goiter. The observations of this study suggests during IDD survey, the effect of concomitant exposure of all the known susceptible progoitrogenic agents present in the environment on thyroid function be evaluated properly.
The authors acknowledge the co-operation received from the staff and students of the studied schools.
Financial support and sponsorship
Thanks are due to University of Calcutta for financial assistance (Grant BI 92).
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rubio IG, Medeiros-Neto G. Mutations of the thyroglobulin gene and its relevance to thyroid disorders. Curr Opin Endocrinol Diabetes Obes 2009;16:373-8.
Li Z, Sturm S, Svejda B, Höger H, Schraml E, Ingolic E, et al.
Anticancer activity of novel extracts from Cautleya gracilis
(Smith) Dandy: Apoptosis in human medullary thyroid carcinoma cells. Anticancer Res 2008;28:2705-13.
Chandra AK, Tripathy S, Ghosh D, Debnath A, Mukhopadhyay S. Iodine nutritional status & prevalence of goitre in Sundarban delta of South 24-Parganas, West Bengal. Indian J Med Res 2005;122:419-24.
Chandra AK, Tripathy S, Ghosh D, Debnath A, Mukhopadhyay S. Goitre prevalence and the state of iodine nutrition in the Sundarban delta of North 24-Parganas in West Benegal. Asia Pac J Clin Nutr 2006;15:357-61.
Cochran WG. Sampling Technique. 3 rd
ed. Calcutta: Wiley Eastern Limited; 1977.
Chandra AK, Bhattacharjee A, Malik T, Ghosh S. Goiter prevalence and iodine nutritional status of school children in a sub-Himalayan Tarai region of eastern Uttar Pradesh. Indian Pediatr 2008;45:469-74.
World Health Organization, United Nations Children′s Emergency Fund, International Council for Control for Iodine Deficiency Disorders. Assessment of Iodine Deficiency Disorders and Monitoring their Elimination.
ed. Geneva, Switzerland: WHO; 2007.
Chandra AK, Singh LH, Debnath A, Tripathy S, Khanam J. Dietary supplies of iodine & thiocyanate in the aetiology of endemic goitre in Imphal East district of Manipur, north east India. Indian J Med Res 2008;128:601-5.
Karmarkar MG, Pandav CS, Krishnamachari KA. Principle and procedure for iodine estimation. A laboratory manual. New Delhi: Indian Council of Medical Research; 1986.
Aldridge WN. The estimation of micro quantities of cyanide and thiocyanate. Analyst 1945;70:474.
Michajlovskij N, Langer P. Studies on relations between thiocyanate formation and goitrogenic properties of foods. I. Preformed thiocyanate content of some foods. Hoppe Seylers Z Physiol Chem 1958;312:26-30.
Titration methods for salt iodine analysis. In: Sullivan KM, Houston E, Gorestein J, Cervinskas J, editors. Monitoring Universal Salt Iodization Programme. Netherlands: UNICEF/ICCIDD/PAMM/WHO; 1995. p. 11.
Rand MC, Greenberg AE, Taras MJ. Hardness. In: Standard Methods for the Examination of Water and Waste Water. 14 th
ed. Washington, DC: American Public Health Association, American Waste Works Association, Water Pollution Control Federation; 1975. p. 200-20.
König F, Andersson M, Hotz K, Aeberli I, Zimmermann MB. Ten repeat collections for urinary iodine from spot samples or 24-hour samples are needed to reliably estimate individual iodine status in women. J Nutr 2011;141:2049-54.
Pearce EN. Iodine in pregnancy: Is salt iodization enough? J Clin Endocrinol Metab 2008;93:2466-8.
Suzuki H, Higuchi T, Sawa K, Ohtaki S, Horiuchi Y. "Endemic coast goitre" in Hokkaido, Japan. Acta Endocrinol (Copenh) 1965;50:161-76.
Li M, Liu DR, Qu CY, Zhang PY, Qian QD, Zhang CD, et al.
Endemic goitre in central China caused by excessive iodine intake. Lancet 1987;2:257-9.
Seal AJ, Creeke PI, Gnat D, Abdalla F, Mirghani Z. Excess dietary iodine intake in long-term African refugees. Public Health Nutr 2006;9:35-9.
Sigurdsson G, Franzson L. Urine excretion of iodine in an Icelandic population. Icelandic Med J 1988;74:179-81.
Zeltser ME, Aldarkhanov BA, Berezhnaya IM, Spernasky GG, Bazarbekova RB, Nurbekova AA, et al
. Iodine deficiency and its clinical manifestation in Kazakhastan. IDD Newsl 1992;8:5-6.
Marwaha RK, Tandon N, Gupta N, Karak AK, Verma K, Kochupillai N. Residual goitre in the postiodization phase: Iodine status, thiocyanate exposure and autoimmunity. Clin Endocrinol (Oxf) 2003;59:672-81.
Chandra AK, Singh LH, Ghosh S, Pearce EN. Role of bamboo-shoot in the pathogenesis of endemic goiter in Manipur, North East India. Endocr Pract 2013;19:36-45.
Chandra AK, Ray I. Dietary supplies of iodine and thiocyanate in the etiology of endemic goiter in Tripura. Indian J Pediatr 2001;68:399-404.
Fukayama H, Nasu M, Murakami S, Sugawara M. Examination of antithyroid effects of smoking products in cultured thyroid follicles: Only thiocyanate is a potent antithyroid agent. Acta Endocrinol (Copenh) 1992;127:520-5.
Stoewsand GS. Bioactive organosulfur phytochemicals in Brassica oleracea
vegetables - A review. Food Chem Toxicol 1995;33:537-43.
Ermans AM, Bourdoux P. Antithyroid sulfurated compounds. In: Gaitan E, editor. Environmental Goitrogensis. Boca Raton, FL: CRC Press; 1989. p. 15-31.
van Middlesworth L. Thiocyanate feeding with low iodine diet causes chronic iodine retention in thyroids of mice. Endocrinology 1985;116:665-70.
Steinmaus C, Miller MD, Cushing L, Blount BC, Smith AH. Combined effects of perchlorate, thiocyanate, and iodine on thyroid function in the National Health and Nutrition Examination Survey 2007-08. Environ Res 2013;123:17-24.
Indian Standard Drinking Water - Specification. (Amendment 1993). First Revision, UDC 628.1.003. IS 10500. New Delhi: Bureau of Indian Standards; 1991.
Langer P. History of goitre. In: Endemic Goitre. WHO Monograph Series. Vol. 44. Geneva: World Health Organization; 1960. p. 9-26.
Murray MM, Ryle JA, Simpson BW, Wilson DC. Thyroid enlargement and other changes related to the mineral content of drinking water with a note on goitre prophylaxis. Br Med Res Counc Memo 1948:18.
Rousset AB, Dunn JT. Thyroid hormone synthesis and secretion. In: The Thyroid and Its Diseases; 2004. Available from: http://www.Thyroidmanager.org/Chapter
2/2-frame.htm. [Last accessed on 2015 Sep 02].
Chandra AK, Goswami H, Sengupta P. Dietary calcium induced cytological and biochemical changes in thyroid. Environ Toxicol Pharmacol 2012;34:454-65.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]
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